The broad, long-term objectives and goal of this program is to build on and extend the current knowledge in the field of stem cell therapy for patients with hemato-lymphoid diseases. While the work in the past 12 years has focused on breast cancer, the current data have had an impact on the numbers of breast cancer patients treated with high dose therapy. However, the infrastructure built and the cohesive interactions of the investigators in this application have remained strong and led to several novel developments. Promising research that may lead to prolonged disease control and possible cures is the central goal of this application. In order to improve progression-free and overall survival, the investigators of this application will utilize a translational research approach bridging the novel experimental observations made in the laboratory to our patients. This program project will focus on the utility of stem cell transplantation as the first building block on which to build further therapies to decrease relapse and improve survival. The theme of this program project focuses on improving the therapeutic results and decreasing the toxicity of stem cell transplantation through a collaborative and integrated approach involving all the investigators in this application. The three specific aims involve vaccine therapy, adoptive immunotherapy in the form of allogeneic stem cell transplantation and pharmacology of the preparatory regimens, tumor drug resistance and methods to circumvent the resistance. Each of these aims utilize the stem cell as the first step upon which to build approaches aimed at enhancing disease control through endogenous or exogenous mechanism. These three aims are supported by two cores: an administrative and research coordination core and a biostatistics and data management core. The hope is to identify the most promising approaches for future studies.